Wobenzym® in the Treatment of Acute Thrombophlebitis
(MU-693204)
Valery M. Koshkin,
M.D., D.M.Sci.Wobenzym® in the Treatment of Acute Thrombophlebitis.
PharmaScript, Kathi-Kobus-Steig 1, D-82515 Wolfratshausen, Germany.
Angiology Laboratory, Department of Surgery, State Medical
University of Russia, Leninsky prospect, 8 Ia, Moscow, 117049 -
Russia
Summary: In a randomised double blind clinical trial phase III (acc.
to German Drug Law) with two parallel groups, it should be
demonstrated in patients with thrombo- or varicophlebitis whether
the enzyme preparation Wobenzym® reduces pain and edema earlier than
a placebo treatment.
119 patients with clinically verified acute thrombophlebitis or
varicophlebitis of a superficial vein of the lower extremity were
taken into this study. 60 patients received the enzyme preparation
and 59 placebo. The data of all patients was evaluable.
Primary investigator was Prof. Valery M. Koshkin, M.D., D.M.Sci.,
Angiology Laboratory, Department of Surgery, State Medical
University of Russia, Leninsky prospect, 8 Ia, Moscow, 117049 -
Russia.
The patients received 10 tablets t.i.d. (= 30 tablets per day). The
therapy lasted 15 days.
At baseline the patients were comparable with regard to age, sex,
height, weight and the symptoms pain, redness, induration, swelling,
sum score of the symptoms, length of the inflammatory vascular
process and time for refilling of the veins (p > 0.05, Wilcoxon-Mann-Whitney-U-test).
The main endpoint for statistical evaluation was the sum score of
the symptoms pain, redness, induration and swelling.
As secondary criteria the other parameters for evaluation of the
efficacy like pain, redness, induration, swelling, length of the
inflammatory vascular process, smallest circumference supramalleolar,
largest calf circumference, knee circumference, circumference 15 cm
above the knee, time for refilling the veins (by light-reflexion-rheography),
the result of therapy and the subjective judgement of efficacy by
the physician and the patients were evaluated. Other secondary
criteria were the laboratory parameters (ESR, white blood cells,
platelets, AST, ALT, g-GT), the subjective judgement of tolerante,
and adverse events caused by the study therapy.
The main endpoint - the sum score of pain, redness, in duration and
swelling - showed a statistically significant difference on the 5%
level (p = 0.033) after 15 days of treatment in favor of the enzyme
treatment.
The judgments of the secondary criteria showed statistically
significant differences in favor of the enzyme treatment with pain
(p = 0.033), the length of the inflammatory vascular process (p =
0.005) and the time for refilling the veins of the affected leg (p =
0.005).
The result of therapy in the enzyme group was on average 2.6 ("good"
to "moderate") and therefore some better than in the placebo group
with 3.0 ("moderate"), but the difference was not statistically
significant (p > 0.05).The efficacy of the drug was judged by the
physician at the end of therapy in the enzyme group with 2.6 ("good"
to "moderate") and in the placebo group with 2.9 ("moderate"). The
patients judged the efficacy as 2.6 ("good" to "moderate") in the
enzyme group and es 2.8 ("moderate") in the placebo group. The
difference between the groups was not statistically significant (p >
0.05).
The tolerance of the therapy was judged by the physician in the
enzyme group as 1.8 ("good") and in the place- bo group as 1.7
("very good" to "good"). The judgments by the patients was similar:
1.9 ("good") in the enzyme group and 1.8 ("good") in the placebo
group. There was no significant difference between the groups (p >
0.05).
Adverse events occurred in either group. Three were documented in the enzyme group and four in the placebo group. The difference between the groups was not statistically significant (p > 0.05). In the enzyme group there was one thrombosis on the contralateral leg, one deep vein thrombosis of the lower extremity and one acute ileofemoral thrombosis. The onset was on average after 7.0 days and they lasted for 7.3 days. The severity of all adverse events was "moderate" and the cause judged as "unknown". In all three patients the study therapy was stopped and twice a symptomatic therapy of the adverse events with heparin was necessary. In two patients residual complaints did not arise and the patient's outcome was without damage. In one patient residual complaints without specification were seen, there was a transitory damage. In the placebo group there were dysphagia, nausea and headache. They started on average after 6.8 days, the duration was one day, and they were "moderate". They were caused in one patient by the study drug, and in three cases the cause was unknown. In one patient the therapy was stopped, in one patient no measures were taken, and in two patients a symptomatic therapy of the adverse event with analgesics was necessary. No residual complaints were seen in any case, and all patients' outcome was without damage.